An Empirical Study on the Effectiveness of Adversarial Examples in Malware Detection

Antivirus vendors and the research community employ Machine Learning(ML)or Deep Learning(DL)-based static analysis techniques for efficient identification of new threats,given the continual emergence of novel malware variants.On the other hand,numerous researchers have reported that Adversarial Examples(AEs),generated by manipulating previously detected malware,can successfully evade ML/DL-based classifiers.Commercial antivirus systems,in particular,have been identified as vulnerable to such AEs.This paper firstly focuses on conducting black-box attacks to circumvent ML/DL-based malware classifiers.Our attack method utilizes seven different perturbations,including Overlay Append,Section Append,and Break Checksum,capitalizing on the ambiguities present in the PE format,as previously employed in evasion attack research.By directly applying the perturbation techniques to PE binaries,our attack method eliminates the need to grapple with the problem-feature space dilemma,a persistent challenge in many evasion attack studies.Being a black-box attack,our method can generate AEs that successfully evade both DL-based and ML-based classifiers.Also,AEs generated by the attack method retain their executability and malicious behavior,eliminating the need for functionality verification.Through thorogh evaluations,we confirmed that the attack method achieves an evasion rate of 65.6%against well-known ML-based malware detectors and can reach a remarkable 99%evasion rate against well-known DL-based malware detectors.Furthermore,our AEs demonstrated the capability to bypass detection by 17%of vendors out of the 64 on VirusTotal(VT).In addition,we propose a defensive approach that utilizes Trend Locality Sensitive Hashing(TLSH)to construct a similarity-based defense model.Through several experiments on the approach,we verified that our defense model can effectively counter AEs generated by the perturbation techniques.In conclusion,our defense model alleviates the limitation of the most promising defense method,adversarial training,which is only effective against the AEs that are included in the training classifiers.

Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients,may mediate immune evasion

BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in HCC.METHODS Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in HCC.Using immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our results.The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint expression.Finally,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining assays.RESULTS Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor prognosis.Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor.In HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation levels.Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup.The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor prognosis.CONCLUSION As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.

Protein tyrosine phosphatase non-receptor Ⅱ:A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma

BACKGROUND The incidence of primary liver cancer is increasing year by year.In 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of cases.HCC is the most common primary liver cancer.China has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese people.The onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when diagnosed.Therefore,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of patients.Protein tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further studied.AIM To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in HCC.METHODS The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and immunoblotting.The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features.Finally,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining.RESULTS The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways,including cancer-related pathways,the Notch signaling pathway,and the MAPK signaling pathway.Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways,such as the epithelial mesenchymal transition process.A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group.CONCLUSION This study investigated PTPN2 from multiple biological perspectives,revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Accurate Diagnosis of SARS-CoV-2 JN.1 by Sanger Sequencing of Receptor-Binding Domain Is Needed for Clinical Evaluation of Its Immune Evasion

Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

面向云安全的基于格的高效属性基加密方案

随着越来越多的企业使用云计算提供的各种数据服务,云安全变得至关重要,而数据的加密和身份访问管理(IAM)是云安全的重要组成部分。密文策略属性基加密(CP-ABE)是一种特殊的公钥加密方案,可以用来解决密文的访问控制问题,适用于身份和访问管理系统。然而现有的属性基加密方案大多不能抵抗量子攻击,并且只能支持单值属性。为了满足身份访问管理中常用的基于属性的访问控制(ABAC)模型的需求,文章基于环上的错误学习问题构造了一个多权威密文策略属性基加密方案。文章所提方案采用键值对形式的属性,并支持析取范式的访问结构,能够实现细粒度的访问控制。同时,该方案允许多个权威去中心化地管理密钥。另外,该方案依赖于evasive LWE假设在多项式环上的变种,该方案被证明具有静态安全性。文章对方案进行了C++语言的实现验证,并进行了性能测试,实验结果表明,该方案具有较高的性能,适合实际应用。

Immune evasion and therapeutic opportunities based on natural killer cells

Natural killer(NK)cells can elicit an immune response against malignantly transformed cells without recognizing antigens,and they also exhibit cytotoxic effects and immune surveillance functions in tumor immunotherapy.Although several studies have shown the promising antitumor effects of NK cells in immunotherapy,their function is often limited in the tumor microenvironment because tumor cells can easily escape NK cell-induced death.Thus,for efficient tumor immunotherapy,the mechanism by which tumor cells escape NK cell-induced cytotoxicity must be fully understood.Various novel molecules and checkpoint receptors that mediate the disruption of NK cells in the tumor microenvironment have been discovered.In this review,we analyze and detail the major activating and inhibitory receptors on the surface of NK cells to delineate the mechanism by which tumor cells suppress NKG2D ligand expression and increase tumor receptor and inhibitory receptor expression[NKG2A,programmed cell death1(PD-1),and T-cell immunoglobulin and immunoreceptor tyrosine inhibitory motif(TIGIT)]on the NK cell surface,and thus inhibit NK cell activity.We also reviewed the current status of treatments based on these surface molecules.By comparing the therapeutic effects related to the treatment status and bypass mechanisms,we attempt to identify optimal single or combined treatments to suggest new treatment strategies for tumor immunotherapy.

Optimal maneuvering strategy of spacecraft evasion based on angles-only measurement and observability analysis

Spacecraft orbit evasion is an effective method to ensure space safety. In the spacecraft’s orbital plane, the space non-cooperate target with autonomous approaching to the spacecraft may have a dangerous rendezvous. To deal with this problem, an optimal maneuvering strategy based on the relative navigation observability degree is proposed with angles-only measurements. A maneuver evasion relative navigation model in the spacecraft’s orbital plane is constructed and the observability measurement criteria with process noise and measurement noise are defined based on the posterior Cramer-Rao lower bound. Further, the optimal maneuver evasion strategy in spacecraft’s orbital plane based on the observability is proposed. The strategy provides a new idea for spacecraft to evade safety threats autonomously. Compared with the spacecraft evasion problem based on the absolute navigation, more accurate evasion results can be obtained. The simulation indicates that this optimal strategy can weaken the system’s observability and reduce the state estimation accuracy of the non-cooperative target, making it impossible for the non-cooperative target to accurately approach the spacecraft.

Delay-CJ:A novel cryptojacking covert attack method based on delayed strategy and its detection

Cryptojacking is a type of resource embezzlement attack,wherein an attacker secretly executes the cryptocurrency mining program in the target host to gain profits.It has been common since 2017,and in fact,it once became the greatest threat to network security.To better prove the attack ability the harm caused by cryptojacking,this paper proposes a new covert browser-based mining attack model named Delay-CJ,this model was deployed in a simulation environment for evaluation.Based on the general framework of cryptojacking,Delay-CJ adds hybrid evasion detection techniques and applies the delayed execution strategy specifically for video websites in the prototype implementation.The results show that the existing detection methods used for testing may become invalid as result of this model.In view of this situation,to achieve a more general and robust detection scheme,we built a cryptojacking detection system named CJDetector,which is based on cryptojacking process features.Specifically,it identifies malicious mining by monitoring CPU usage and analyzing the function call information.This system not only effectively detects the attack in our example but also has universal applicability.The recognition accuracy of CJDetector reaches 99.33%.Finally,we tested the web pages in Alexa 50K websites to investigate cryptojacking activity in the real network.We found that although cryptojacking is indeed on the decline,it remains a part of network security threats that cannot be ignored.

Circulating tumor cells: Biological features and survival mechanisms

Circulating tumor cells(CTCs)are neoplastic cells that are detached from primary tumors and enter circulation.Enumeration and characterization of CTCs are of significance in cancer diagnosis,prognosis,and treatment monitoring.CTC survival in the bloodstream is a limiting step for the development of metastases in distant organs.Recent technological advances,especially in single-cell molecular analyses have uncovered heterogeneous CTC survival mechanisms.Undergoing epithelial-to-mesenchymal transition(EMT),increasing stem cell-like properties,and forming cell clusters enable CTCs to adapt to the harsh microenvironment of the circulation.Expressing and releasing several immunosuppressive molecules help CTCs escape from anti-cancer immune mechanisms.This review article summarizes the biological characteristics of CTCs and focuses on the recent understanding of the mechanisms by which CTCs survive in circulation.Additionally,the clinical and therapeutic implications of CTCs are discussed.

Intracellular life of protozoan Toxoplasma gondii:Parasitophorous vacuole establishment and survival strategies

Toxoplasma gondii is a protozoan of worldwide distribution and the agent of toxoplasmosis.It is estimated that 30%–50%of the world population could be infected with this parasite.Although the infection in immunocompetent individuals is mostly asymptomatic,the disease in immunosuppressed and pregnant is a risk condition.As a member of the phylum Apicomplexa,T.gondii has an obligatory intracellular lifestyle;therefore,invading a host cell and establishing it inside a parasitophorous vacuole(PV)are mandatories for the survival of this parasite.The construction of a perfect intracellular niche for T.gondii requires the secretion of an arsenal of proteins from unique secretory organelles.These proteins will remodel the vacuolar environment and the host cell organization and functions,allowing the parasite to access essential nutrients and stay“invisible”inside a host cell.In the present review,we will discuss the main steps involved in the PV formation and its differentiation to tissue cyst,focusing mainly on the strategies employed in the acquisition of nutrients and proteins involved in host cell modification.

Research Hotspot and Application Status of Immune Evasion Mechanism in Ovarian Cancer

Ovarian cancer is one of the three major malignant tumors in gynecology, with increasing incidence and mortality rates. Currently, the main treatment methods remain surgical intervention in combination with chemotherapy. However, due to its high recurrence rate and the risk of drug resistance, the overall prognosis is poor. Ovarian cancer has been identified as an immunegenic tumor, and in recent years, with the continued advancement of research into immune evasion mechanisms, immunotherapy has emerged as a groundbreaking treatment modality. This article will focus on the immune escape mechanisms and their application in ovarian cancer, providing a comprehensive overview of its current status and the challenges it faces.

Mechanisms of drug resistance in colon cancer and its therapeutic strategies

Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATPbinding cassette(ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics.

Interplay between hepatitis B virus and the innate immune responses:implications for new therapeutic strategies

Hepatitis B virus(HBV) infection is still a worldwide health problem;however,the current antiviral therapies for chronic hepatitis B are limited in efficacy.The outcome of HBV infection is thought to be the result of complex interactions between the HBV and the host immune system.While the role of the adaptive immune responses in the resolution of HBV infection has been well characterized,the contribution of innate immune mechanisms remains elusive until recent evidence implicates that HBV appears to activate the innate immune response and this response is important for controlling HBV infection.Here,we review our current understanding of innate immune responses to HBV infection and the multifaceted evasion by the virus and discuss the potential strategies to combat chronic HBV infection via induction and restoration of host innate antiviral responses.

Recent advances in immunotherapy for hepatocellular carcinoma

Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions.Conventional systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory.Data sources:Literature search was conducted in Pub Med for relevant articles published before January 2021.The search aimed to identify recent developments in immune-based treatment approaches for HCC.Information of clinical trials was obtained from https://clinicaltrials.gov/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC treatment.Besides,combination ICIs have also got accelerated FDA approval recently.Immune-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival benefits.In addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical trials.Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs.Conclusions:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years.However,challenges such as low response rate and acquired resistance in previously respondent patients still exist.Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.

Natural killer cells in hepatitis C:Current progress

Patients infected with the hepatitis C virus(HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer(NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-α-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection.

The 150 most important questions in cancer research and clinical oncology series:questions 50-56

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, seven more questions are presented as followed. Question50. When tumor cells spread from primary site to distant sites, are they required to be "trained" or "armed" in the bone marrow niche prior to colonizing soft tissues? Question 51. Are there tipping points during cancer progression which can be identified for manipulation? Question 52. Can we replace molecular biomarkers by network biomarkers?Question 53. Are conventional inhibitors of key cellular processes such as cell proliferation and differentiation more effective than targeted chemotherapeutics that antagonize the downstream cell signaling network via cell-surface receptors such as epidermal growth factor receptor(EGFR), vascular endothelial growth factor receptor(VEGFR) and c-Met, or intracellular receptors such as androgen receptor(AR) and estrogen receptor(ER), by drugs like erlotinib,sunitinib and cabozantinib, or enzalutamide and tomoxifen? Question 54. How can we robustly identify the candidate causal event of somatic genome alteration(SGA) by using computational approach? Question 55. How can we systematically reveal the immune evasion mechanism exploited by each tumor and utilize such information to guide targeted therapy to restore immune sensitivity? Question 56. Can the nasopharyngeal carcinoma(NPC) patients with sarcomatoid carcinoma(SC) subtype benefit from more specific targeted therapy?

Hepatitis B virus-persistent infection and innate immunity defect: Cell-related or virus-related?

The outcomes of hepatitis B virus(HBV) infection are closely related to the age at which infection was acquired. Infection acquired in adult life tends to be selflimited, in contrast to perinatal acquirement, for which chronic persistence of the HBV is a general outcome. Innate immunity plays an indispensable role in early virus infection, facilitating virus clearance. However, it has been reported that HBV is under-recognized and poorly eliminated by the innate immune system in the early stages of infection, possibly explaining the long-lasting persistence of viremia afterwards. Furthermore, due to the existence of covalently closed circular DNA, chronic HBV clearance is very difficult, even when patients are given interferon-α and nucleotide/nucleoside analogs for antiviral therapy. The mechanism by which HBV evades innate immune recognition and establishes persistent infection remains a subject of debate. Besides, some researchers are becoming more interested in how to eradicate chronic HBV infection by restoring or boosting innate immunity. This review aimed to summarize the current knowledge on how intrahepatocyte signaling pathways and innate immune cells act after the onset of HBV infection and how these actions are related to the persistence of HBV. We anticipate the insights presented herein to be helpful for future development of novel immune therapeutic strategies to fight HBV infection.

Fibroblasts, an inconspicuous but essential player in colon cancer development and progression

Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs.

Bioinformatics analysis for structure and function of CPR of Plasmodium falciparum

Objective:To analyse the structure and function of NADPH-cytochrome p450 reductase(CYPOR or CPR) from Plasmodium falciparum(Pf),and to predict its’ drug target and vaccine target. Methods:The structure,function,drug target and vaccine target of CPR from Plasmodium falciparum were analyzed and predicted by bioinformatics methods.Results:PfCPR,which was older CPR,had close relationship with the CPR from other Plasmodium species,but it was distant from its hosts,such as Homo sapiens and Anopheles.PfCPR was located in the cellular nucleus of Plasmodium falciparum.335aa-352aa and 591aa - 608aa were inserted the interior side of the nuclear membrane,while 151aa-265aa was located in the nucleolus organizer regions.PfCPR had 40 function sites and 44 protein-protein binding sites in amino acid sequence.The teriary structure of laa-700aa was forcep-shaped with wings.15 segments of PfCPR had no homology with Homo sapien CPR and most were exposed on the surface of the protein.These segments had 25 protein-protein binding sites.While 13 other segments all possessed function sites. Conclusions:The evolution or genesis of Plasmodium falciparum is earlier than those of Homo sapiens.PfCPR is a possible resistance site of antimalarial drug and may involve immune evasion, which is associated with parasite of sporozoite in hepatocytes.PfCPR is unsuitable as vaccine target,but it has at least 13 ideal drug targets.